THIS IS A SHANNON AWARD PROVIDING PARTIAL SUPPORT FOR THE RESEARCH PROJECTS THAT FALL SHORT OF THE ASSIGNED INSTITUTE'S FUNDING RANGE BUT ARE IN THE MARGIN OF EXCELLENCE. THE SHANNON AWARD IS INTENDED TO PROVIDE SUPPORT TO TEST THE FEASIBILITY OF THE APPROACH; DEVELOP FURTHER TESTS AND REFINE RESEARCH TECHNIQUES; PERFORM SECONDARY ANALYSIS OR AVAILABLE DATA SETS; OR CONDUCT DISCRETE PROJECTS THAT CAN DEMONSTRATE THE PI'S RESEARCH CAPABILITIES OR LEND ADDITIONAL WEIGHT TO AN ALREADY MERITORIOUS APPLICATION. THE ABSTRACT BELOW IS TAKEN FROM THE ORIGINAL DOCUMENT SUBMITTED BY THE PRINCIPAL INVESTIGATOR. DESCRIPTION (adapted from investigator's abstract): This is a proposal to investigate the role of a novel gene family. The long term objective of this proposal is to understand the function of the disintegrin protein family, some members of which may be involved in cell adhesion. Disintegrins are related to snake venom proteins such as kistrin and echistatin as well as the sperm PH-30 (fertilin a and B) proteins which are involved in sperm-egg membrane binding and fusion. The investigator proposes that there is a family of disintegrin proteins which may mediate important cellular interactions. The investigator wishes to concentrate on one recently cloned member of this family, MDC4. This molecule has a predicted transmembrane domain as well as a metalloprotease domain, a disintegrin domain, a potential fusion peptide domain, and potential intracellular src homology 3 domains. The main focus of the proposal is to test the hypothesis that MDC4 is a cell adhesion molecule, perhaps a ligand for integrins, and plays a role in cell-cell adhesion. Five specific aims are elaborated: first to develop adhesion assays where the MDC4 protein is expressed recombinantly in target cells which will then be assayed for their adhesion properties. Second, it is proposed to study mouse skeletal muscle development using the C2C12 mouse cell line which can be induced to undergo differentiation, and to study the role of MDC4 in this process. Third, it is proposed to generate a mouse with targeted deletion of the MDC4 gene to establish whether MDC4 plays a vital role during embryogenesis or postnatal life. Fourth, the Principal Investigator will seek to identify the ligand for MDC4; the hypothesis driving this proposal is that the ligand will be a member of the integrin family. Last, the Principal Investigator will investigate interactions of the cytoplasmic tail of MDC4 with other cellular proteins using affinity purification techniques and the yeast two-hybrid system.